crossing96/oncoscreening huggingface dataset:
Prospective Assessment of VI-RADS with Muscle Invasion in Urinary Bladder Cancer and Its Implication on Re-Resection/Restaging TURBT Patients.	BACKGROUND: Bladder cancer (BCa) diagnosis relies on distinguishing muscle-invasive bladder cancer (MIBC) from non-muscle-invasive bladder cancer (NMIBC) forms. Transurethral resection of the bladder tumor (TURBT) is a standard procedure for initial staging and treatment. The Vesical Imaging-Reporting and Data System (VI-RADS) enhances diagnostic accuracy for muscle invasiveness through advanced imaging techniques, potentially reducing reliance on repeat TURBT and improving patient management. OBJECTIVE: We aimed to evaluate the role of VI-RADS in predicting muscle invasiveness in BCa and its potential to predict adverse pathology in high-risk NMIBC to avoid unnecessary repeat TURBT procedures. METHODS: In this prospective study, we included 62 patients over the age of 18 years who underwent TURBT. In a secondary phase, patients selected for restaging TURBT (re-TURBT) were included, but those with T2 tumors or low-risk NMIBC were excluded. Multiparametric magnetic resonance imaging (MRI) examinations were scored by a radiologist using the VI-RADS 5 method, while a pathologist analyzed TURBT and re-TURBT samples for accurate staging. Statistical analysis evaluated the role of VI-RADS in BCa staging. RESULTS: The VI-RADS score was the only predictive factor for muscle invasion in multivariate analysis. Setting the VI-RADS score at >3 resulted in the highest sensitivity, specificity, and diagnostic accuracy, with values of 67.0%, 89.0%, and 78%, respectively. The receiver operating characteristic area under the curve score for VI-RADS for muscle invasion was 85% for stage Ta, 61% for stage T1, and 88% for stage T2, which shows the utility of VI-RADS in the predictiveness of MIBC/NMIBC. CONCLUSION: VI-RADS is effective in stratifying BCa patients by predicting muscle invasiveness and identifying NMIBC cases that may not need repeat TURBT.	bladder
MFAP3L predicts tumor microenvironment status, molecular subtypes and clinical benefit in patients with bladder cancer.	Bladder cancer (BLCA), ranking as the tenth most prevalent malignancy globally, imposes a substantial public health and socio-economic challenge. Despite ongoing efforts by urologists to identify novel molecular subtypes and treatment paradigms, the intrinsic heterogeneity of BLCA continues to obstruct the efficacy of current diagnostic and therapeutic evaluations, leaving a gap in the comprehensive management of BLCA. This necessitates an in-depth investigation into the BLCA tumor microenvironment (TME) to identify pivotal molecules like MFAP3L. Our research concentrated on MFAP3L, commencing with a pan-cancer analysis of its immune profile. We discovered that MFAP3L exhibits a significant negative correlation with numerous immune components and markers in BLCA, a trend not observed in other cancer types. Within the TCGA-BLCA cohort, patients were classified into High-MFAP3L and Low-MFAP3L groups according to their MFAP3L transcript levels. Our exploration into the BLCA TME delved into immune infiltration, molecular subtype patterns, and treatment preferences within these MFAP3L groups. High MFAP3L expression was linked to favorable prognoses, luminal subtypes, and low immune infiltration, inversely associated with various immune molecules and characteristics. Additionally, high MFAP3L expressors exhibited diminished immune checkpoint levels, suggesting enhanced immunotherapy tolerance and sensitivity to oncogenic pathway targeting. Conversely, low MFAP3L expression correlated with poor outcomes, basal subtypes, increased immune infiltration, and heightened gene mutation rates, alongside sensitivity to radiotherapy, EGFR-targeted treatments, and immunotherapy. Hence, MFAP3L emerges as a critical yet underexplored gene in BLCA, offering insights into immune status within the TME and aiding in molecular subtyping and therapeutic decision-making.	bladder
Oncological outcomes of organ-sparing cystectomy versus standard radical cystectomy in male patients diagnosed with bladder cancer.	PURPOSE: To compare the oncological outcomes between standard radical cystectomy (SRC) and organ-sparing cystectomy (OSC) in male patients diagnosed with bladder cancer. METHODS: Patients with stage Ta-T3 bladder cancer who underwent OSC or SRC were identified from the Surveillance, Epidemiology, and End Results (SEER) database between 2004 and 2015. The association between preoperative factors and the implementation of OSC was analyzed using logistic regression. Propensity score matching (PSM) was employed to balance baseline characteristics between the two groups. Patients' overall survival (OS) and cancer-specific survival (CSS) were estimated using the Kaplan-Meier method. Subgroup analyses based on the T stage were also conducted. RESULTS: A total of 7264 patients were included, with 96.8% (7033 patients) receiving SRC and 3.2% (231 patients) receiving OSC. Patients with higher T stages and high-grade tumors were less likely to undergo OSC. After PSM, OSC was associated with significantly worse OS and CSS than SRC. Subgroup analysis revealed that OSC did not lead to worse OS and CSS in non-muscle invasive bladder cancer and T2 stage patients, but it resulted in significantly worse outcomes in T3 stage patients. CONCLUSION: Our study indicates that OSC is associated with poorer oncological outcomes compared to SRC, particularly in patients with advanced-stage tumors. These findings suggest the need for stringent selection criteria for OSC in bladder cancer patients. Given the negative impact on prognosis, stage T3 should potentially be considered a contraindication for OSC. Further evidence is required to confirm these assertions.	bladder
A 3-arm randomized control trial to compare the efficacy of re-circulant hyperthermic intravesical chemotherapy versus conventional intravesical mitomycin C and BCG therapy for intermediate-risk non-muscle invasive bladder cancer.	INTRODUCTION: To evaluate the efficacy and side effects of re-circulant hyperthermic intravesical chemotherapy versus conventional treatments for intermediate risk non-muscle invasive bladder cancer (NMIBC). METHODS: A randomized 3-arm, parallel group trial was conducted at a single tertiary care centre. 135 patients with low-grade intermediate-risk cancer, having undergone complete resection of bladder tumor were included. Patients were assigned 1:1:1, to receive intra-vesical chemo-hyperthermia (C-HT), mitomycin-C (MMC) or BCG therapy. There was no treatment crossover. Patients were followed up with check cystoscopy every 3 months for histopathological recurrence. RESULTS: The three arms were comparable in terms of age, gender, tumor size, number of tumors and clinical stage or grade of tumors. Mean tumor size was 2.58 (± 0.88) cm and the mean number of tumors resected was 2.04 (± 1.02) (Range 1-5). There was no significant difference between the various groups for tumor recurrence (χ2 = 1.96, p = 0.375) or time to recurrence (13.6 vs. 10.8 vs. 9.8 months, p = 0.844) though incidence of non-healing necrotic area was higher with C-HT (22.2% vs. 11.1% and 4.8%, χ2 = 6.093, p = 0.048). Median (IQR) follow up period was 26 (12-52) months. Treatment discontinuation or drug intolerance was significantly higher in BCG arm (p = 0.03). CONCLUSIONS: Intravesical C-HT with MMC, conventional MMC and BCG are equally effective and comparable alternatives for intravesical therapy in low-grade intermediate-risk NMIBC. Higher incidence of non-healing resection site with C-HT and higher local symptoms with BCG are a concern.	bladder
A luminal non-coding RNA-based genomic classifier confirms favourable outcomes in patients with clinically organ-confined bladder cancer treated with radical cystectomy.	OBJECTIVE: To further evaluate a genomic classifier (GC) in a cohort of patients undergoing radical cystectomy (RC), as long non-coding RNA (lncRNA)-based genomic profiling has suggested utility in identifying a distinct tumour subgroup corresponding to a favourable prognosis in patients with bladder cancer. PATIENTS AND METHODS: Transcriptome-wide expression profiling using Decipher Bladder was performed on transurethral resection of bladder tumour samples from a cohort of patients with high-grade, clinically organ-confined (cTa-T2N0M0) urothelial carcinoma (UC) who subsequently underwent RC without any neoadjuvant therapy (n = 226). The lncRNA-based luminal favourable status was determined using a previously developed GC. The primary endpoint was overall survival (OS) after RC. Secondary endpoints included cancer-specific mortality and upstaging at RC. RESULTS: In the study, 134 patients were clinical non-muscle-invasive bladder cancer (cTa/Tis/T1) and 92 patients were cT2. We identified 60 patients with luminal favourable subtype, all of which showed robust gene expression patterns associated with less aggressive bladder cancer biology. On multivariate analysis, patients with the luminal favourable subtype (vs without) were significantly associated with lower odds of upstaging to pathological (p)T3+ disease (odds ratio [OR] 0.32, 95% confidence interval [CI] 0.12-0.82; P = 0.02), any upstaging (OR 0.41, 95% CI 0.20-0.83; P = 0.01), and any upstaging and/or pN+ (OR 0.50, 95% CI 0.25-1.00; P = 0.05). Luminal favourable bladder cancer was significantly associated with better OS (hazard ratio 0.33, 95% CI 0.15-0.74; P = 0.007). CONCLUSIONS: This study validates the performance of the GC for identifying UCs with a luminal favourable subtype, harbouring less aggressive tumour biology.	bladder
Exploring the oncogenic role of RGS19 in bladder cancer progression and prognosis.	This study investigates the role of autophagy-related genes (ARGs) in bladder cancer (BLCA), focusing on the regulator of G protein signaling 19 (RGS19). Using data from The Cancer Genome Atlas (TCGA) and the Human Autophagy Database (HADb), we identified RGS19 as significantly upregulated and linked to poor prognosis in BLCA. Kaplan-Meier survival analysis confirmed its association with increased mortality and. In vitro, RGS19 knockdown in BLCA cell lines inhibited proliferation, migration, and invasion, while inducing apoptosis and autophagy. Transmission electron microscopy showed autophagic structures in RGS19-silenced cells. In vivo, a xenograft mouse model demonstrated reduced tumor growth with RGS19 knockdown. Immunohistochemical (IHC) analysis revealed decreased Ki67 and increased autophagy markers in tumors with reduced RGS19. Pathway analysis suggested RGS19 acts through the cGMP-PKG signaling pathway, validated by altered expression of soluble guanylate cyclase (sGC), protein kinase G (PKG1), phosphodiesterase 5 A (PDE5A), vasodilator-stimulated phosphoprotein (VASP), and phosphorylated VASP (p-VASP) upon RGS19 knockdown. These results highlight RGS19 as a potential biomarker and therapeutic target in BLCA.	bladder
SPOP downregulation promotes bladder cancer progression based on cancer cell-macrophage crosstalk via STAT3/CCL2/IL-6 axis and is regulated by VEZF1.	Background: Cancer cells are intimately intertwined with tumor microenvironment (TME), fostering a symbiotic relationship propelling cancer progression. However, the interaction between cancer cells and tumor-associated macrophages (TAMs) in urothelial bladder cancer (UBC) remains poorly understood. Methods: UBC cell lines (5637, T24 and SW780), along with a monocytic cell line (U937) capable of differentiating into macrophage, were used in a co-culture system for cell proliferation and stemness by MTT, sphere formation assays. VEZF1/SPOP/STAT3/CCL2/ IL-6 axis was determined by luciferase reporter, ChIP, RNA-seq, co-IP, in vitro ubiquitination, RT-qPCR array and ELISA analyses. Results: We observed the frequent downregulation of SPOP, an E3 ubiquitin ligase, was positively associated with tumor progression and TAM infiltration in UBC patients and T24 xenografts. Cancer cell-TAM crosstalk promoting tumor aggressiveness was demonstrated dependent on SPOP deficiency: 1) In UBC cells, STAT3 was identified as a novel substrate of SPOP, and SPOP deficiency increased STAT3 protein stability, elevated chemokine CCL2 secretion, which induced chemotaxis and M2 polarization of macrophage; 2) In co-cultured macrophages, IL-6 secretion enhanced UBC cell proliferation and stemness. Additionally, transcription factor VEZF1 could directly activate SPOP transcription, and its overexpression suppressed the above effects in UBC cells. Conclusions: A pivotal role of SPOP in maintaining UBC stemness and remodeling immunosuppressive TME was revealed. Both the intrinsic signaling (dysregulated VEZF1/SPOP/STAT3 axis) and the extrinsic cues from TME (CCL2-IL-6 axis based on macrophages) promoted UBC progression. Targeting this crosstalk may offer a promising therapeutic strategy for UBC patients with SPOP deficiency.	bladder
Silencing CCT3 induces ferroptosis through the NOD1-NF-κB signaling pathway in bladder cancer.	Bladder cancer (BCa) is a lethal malignancy of the urinary system and exhibits a poor prognosis. Chaperonin-containing tailless complex polypeptide 1 subunit 3 (CCT3) acts as an oncogene in various tumors, whereas its effect on BCa remains unknown. We identified the ferroptosis-associated differentially expressed genes through bioinformatic analysis and selected CCT3 for further verification. The levels of cell viability, apoptosis, migration, invasion, and proliferation were measured to clarify the effect of silencing CCT3 on BCa cells. Then we evaluated the role of CCT3 knockdown in vivo. Ferroptosis was assessed by the expression detection of the ferroptosis-related proteins. The underlying mechanism was predicted by RNA sequencing and verified by an agonist for nucleotide-binding and oligomerization domain 1 (NOD1). Western blotting was conducted to detect the protein expression of NOD1, nuclear factor kappa B (NF-κB) inhibitor alpha (IκBα), and phospho-IκBα (p-IκBα). In vitro, down-regulation of CCT3 suppressed the cell viability, migration, invasion, and proliferation, as well as induced apoptosis of BCa cells. In vivo, silencing CCT3 elevated the body weight of mice and suppressed the BCa progression. In addition, CCT3 knockdown could induce ferroptosis in vitro and in vivo. CCT3 knockdown suppressed the expression of NOD1 and p-IκBα/IκBα and the NOD1 agonist could reverse the effect of CCT3 suppression on BCa in vitro and in vivo. In summary, our findings demonstrate that silencing CCT3 inhibits BCa via induction of ferroptosis and suppression of the NOD1-NF-κB pathway.	bladder
Association of Tumor Mutational Burden and PD-L1 with the Efficacy of Pembrolizumab with or without Chemotherapy versus Chemotherapy in Advanced Urothelial Carcinoma.	PURPOSE: The three-arm, phase III KEYNOTE-361 study did not meet its dual primary endpoints of progression-free survival (PFS) or overall survival (OS) with first-line pembrolizumab plus chemotherapy versus chemotherapy in advanced urothelial carcinoma. This prespecified exploratory analysis assessed the association of tumor mutational burden (TMB) and PD-L1 combined positive score (CPS) with clinical outcomes. PATIENTS AND METHODS: TMB and PD-L1 CPS were determined via whole-exome sequencing and PD-L1 IHC 22C3 pharmDx, respectively. The association was evaluated in each treatment arm using logistic regression [objective response rate (ORR)] and Cox proportional hazards regression models (PFS and OS); one-sided (pembrolizumab monotherapy; pembrolizumab plus chemotherapy) and two-sided (chemotherapy) nominal P values were calculated. Significance was prespecified at α = 0.05 without multiplicity adjustment. Efficacy was evaluated by prespecified cutoffs of 175 mutations/exome (TMB) and CPS 10 (PD-L1). RESULTS: Of the 993 treated patients, 820 (82.6%) and 993 (100%) had evaluable TMB and CPS data, respectively. Continuous TMB was positively associated with ORR, PFS, and OS for pembrolizumab monotherapy (one-sided P < 0.001, P < 0.001, and P = 0.007, respectively); PFS and OS for pembrolizumab plus chemotherapy (one-sided P = 0.007 and P = 0.010, respectively); and OS for chemotherapy alone (two-sided P = 0.040). Continuous PD-L1 CPS showed evidence of anticipated association with ORR and PFS for pembrolizumab monotherapy. The subgroup with TMB ≥175 mutations/exome and PD-L1 CPS ≥10 had the highest PFS and OS improvements with pembrolizumab alone or with chemotherapy versus chemotherapy alone. CONCLUSIONS: These data suggest that TMB may be predictive of the response to pembrolizumab alone or with chemotherapy in advanced urothelial carcinoma.	bladder
Altered immunophenotypic expression in the peripheral bladder cancer immune landscape.	Treatments targeting the immune system only benefit a subset of patients with bladder cancer (BC). Biomarkers predictive of BC progression and response to specific therapeutic interventions are required. We evaluated whether peripheral blood immune subsets and expression of clinically relevant immune checkpoint markers are associated with clinicopathologic features of BC. Peripheral blood mononuclear cells isolated from blood collected from 23 patients with BC and 9 age-matched unaffected-by-cancer control donors were assessed using a 21-parameter flow cytometry panel composed of markers of T, B, natural killer and myeloid populations and immune checkpoint markers. Patients with BC had significantly lower numbers of circulating CD19(+) B cells and elevated circulating CD4(+)CD8(+) T cells compared with the control cohort. Immune checkpoint markers programmed cell death protein 1 (PD-1) and T-cell immunoglobulin and mucin-domain containing-3 (TIM-3) were elevated in the total peripheral immune cell population in patients with BC. Within the BC cohort, PD-1 expression in T and myeloid cells was elevated in muscle-invasive compared with non-muscle-invasive disease. In addition, elevated T, B and myeloid PD-1 cell surface expression was significantly associated with tumor stage, suggesting that measures of peripheral immune cell exhaustion may be a predictor of tumor progression in BC. Finally, positive correlations between expression levels of the various immune checkpoints both overall and within key peripheral blood immune subsets collected from patients with BC were observed, highlighting likely coregulation of peripheral immune checkpoint expression. The peripheral blood immunophenotype in patients with BC is altered compared with cancer-free individuals. Understanding this dysregulated immune profile will contribute to the identification of diagnostic and prognostic indicators to guide effective immune-targeted, personalized treatments.	bladder
UPLC-Q-TOF/MS-based urine metabolomics for the diagnosis and staging of bladder cancer.	BACKGROUND: Bladder cancer (BC) is a common malignant tumour of the urinary system. Currently, the gold standard for diagnosing BC is cystoscopy, but it is an invasive examination that can lead to a certain psychological burden on the patient. In this study, we aimed to identify non-invasive potential metabolic biomarkers that could improve the diagnostic accuracy of bladder cancer. METHODS: Urine from 30 healthy people and 50 BC patients, including 40 non-muscle-invasive bladder cancer (NMIBC) patients and 10 muscle-invasive bladder cancer (MIBC) patients, were analyzed by liquid chromatography coupled with mass spectrometry to identify potential diagnostic metabolites. Binary Logistic regression was used to construct biomarker panels. Correlation analysis and construction of compound-reaction-enzyme-gene network were also performed to explore the possible mechanisms of BC development. RESULTS: Twenty-six metabolites were identified for differentiating BC patients from healthy controls, and eight metabolites were identified for differentiating NMIBC patients form MIBC patients. The biomarker panel consisting of urate, 4-Androstene-3α, 17β-diol and 3-Indoxyl sulfate can distinguish well between BC patients and healthy controls, with an area under the ROC curve (AUC) value of 0.983. And the biomarker panel consisting of L-Octanoylcarnitine, γ-Glutamylleucine, and heptanoylcarnitine for distinguishing NMIBC patients from MIBC patients had an AUC value of 0.941. CONCLUSIONS: The diagnostic capability of the biomarker panels are superior to that of any single potential biomarker. This panel significantly benefits bladder cancer diagnostics and reveals insight into bladder cancer pathogenesis.	bladder
Appearance of New Lesions Associate With Poor Prognosis in Pembrolizumab-Treated Urothelial Carcinoma.	OBJECTIVES: This study investigated the variations in response patterns, including target lesion enlargement and the emergence of new lesions, in patients with urothelial carcinoma receiving pembrolizumab therapy and assessed the impact of new lesions on patient outcomes. METHODS: This retrospective analysis included patients with urothelial carcinoma treated with pembrolizumab following platinum failure. Response Evaluation Criteria in Solid Tumors criteria were used to assess the target lesion size and appearance of new lesions. Patients were categorized into 2 groups: the primary progressive disease (PD) group, consisting of patients who progressed within 28 to 84 days of treatment initiation, and the secondary PD group, consisting of patients who progressed more than 84 days after treatment initiation. Survival analyses were performed to evaluate the impact of new lesions on patient outcomes. RESULTS: In this study, 42 patients experienced primary PD, and 37 experienced secondary PD. Among patients with primary PD, 64.3%, 73.8%, 45.2% had an increase of 20% or more in target lesion size, newly emerged lesions, and both an increase in target lesion size and new lesions, respectively. Kaplan-Meier analysis revealed that patients with primary PD and new lesions had significantly shorter overall survival after PD than those with only target lesion growth and those with secondary PD (both P < .001). CONCLUSION: This study revealed the heterogeneity of response patterns during pembrolizumab therapy in patients with urothelial carcinoma and primary pembrolizumab resistance and the presence of new lesions early in treatment. Earlier imaging evaluation should be performed to assess for the appearance of new lesions, leading to sequential treatment.	bladder
Gefitinib Reverses PD-L1-Mediated Immunosuppression Induced by Long-term Glutamine Blockade in Bladder Cancer.	Glutamine is a major energy source for tumor cells, and blocking glutamine metabolism is being investigated as a promising strategy for cancer therapy. However, the antitumor effect of glutamine blockade in bladder cancer remains unclear, necessitating further investigation. In this study, we demonstrated that glutamine metabolism was involved in the malignant progression of bladder cancer. Treatment with the glutamine antagonist 6-diazo-5-oxo-L-norleucine (DON) inhibited the growth of bladder cancer cells in vitro in several ways. In addition, we observed inhibition of tumor growth in bladder cancer-bearing mice by using JHU083, a prodrug that was designed to prevent DON-induced toxicity. However, the antitumor immune effect of T cells changed from activation to inhibition as the administrated time extended. We found that both in vitro treatment with DON and in vivo prolonged administration of JHU083 led to the upregulation of PD-L1 in bladder cancer cells. Mechanistically, glutamine blockade upregulated PD-L1 expression in bladder cancer cells by accumulating reactive oxygen species, subsequently activating the EGFR/ERK/C-Jun signaling pathway. Combination treatment of JHU083 and gefitinib reversed the upregulation of PD-L1 in bladder cancer cells induced by prolonged glutamine blockade, resulting in the alleviation of T-cell immunosuppression and a significant improvement in therapeutic outcome. These preclinical findings show promise for glutamine metabolism targeting as a viable therapeutic strategy for bladder cancer, with the potential for further enhancement through combined treatment with gefitinib.	bladder